title: Biotransformation of natural compounds. Oxido-reduction of Sch-642305 by Aspergillus ochraceus ATCC 1009.
abstract: Sch-642305 is the major compound produced by the endophytic fungi Phomopsis sp. CMU-LMA. Incubation of Sch-642305 with Aspergillus ochraceus ATCC 1009 resting cells leads to three new derivatives through an oxido-reduction of the six-membered ring of the molecule. Reduction of the double bound leads to compound (1), which subsequently undergoes carbonyl reduction to (2) and ring hydroxylation to (3). According to the previously solved crystal structure of Sch-642305 coupled with (1)H NMR NOE correlation and the crystal structure of compound 1, the absolute configurations of the new derivatives were established. In contrast to the parent compound Sch-642305, compound (1) exhibits antimicrobial activity against gram-negative bacteria. Furthermore, while all derivatives exhibit cytotoxic activity against various cancer cell lines, compound (2) achieved an IC(50) of 4 nM against human myelogenous leukemia K 562, compared to 20 nM for the parent Sch-642305.
authors.affiliation: Centre de Recherche de Gif, Institut de Chimie des Substances Naturelles, C.N.R.S., Avenue de la Terrasse, 91198 Gif-sur-Yvette Cedex, France.
authors.forename: Emilie
authors.initials: E
authors.lastname: Adelin
authors.forename: Claudine
authors.initials: C
authors.lastname: Servy
authors.forename: Sylvie
authors.initials: S
authors.lastname: Cortial
authors.forename: Hélène
authors.initials: H
authors.lastname: Lévaique
authors.forename: Jean François
authors.initials: JF
authors.lastname: Gallard
authors.forename: Marie-Thérèse
authors.initials: MT
authors.lastname: Martin
authors.forename: Pascal
authors.initials: P
authors.lastname: Retailleau
authors.forename: Boonsom
authors.initials: B
authors.lastname: Bussaban
authors.forename: Saisamorn
authors.initials: S
authors.lastname: Lumyong
authors.forename: Jamal
authors.initials: J
authors.lastname: Ouazzani
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000493:pharmacokinetics / Q000633:toxicity; D001235:Aspergillus ochraceus / Q000378:metabolism*; D001711:Biotransformation; D045744:Cell Line, Tumor; D018360:Crystallography, X-Ray; D006801:Humans; D007700:Kinetics; D018942:Macrolides / Q000737:chemistry* / Q000378:metabolism* / Q000493:pharmacokinetics / Q000633:toxicity; D008826:Microbial Sensitivity Tests; D008968:Molecular Conformation; D010084:Oxidation-Reduction
chemical_list: C559484:12-hydroxy-4-methyldecahydro-1H-benzo(d)oxecine-2,9-dione; D000900:Anti-Bacterial Agents; D018942:Macrolides; C482741:Sch 642305